2-237534764-G-C

Variant names:

• chr2-237534764-G-C
• rs2292885
• NM_024101.7:c.1104+117G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024101.7(MLPH):​c.1104+117G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 856,520 control chromosomes in the GnomAD database, including 49,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (15299 hom., cov: 32)
  • Exomes 𝑓: 0.30 (34180 hom.)
• Consequence: MLPH NM_024101.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.947
• Publications: 11 publications found

Genes affected

MLPH (HGNC:29643): (melanophilin) This gene encodes a member of the exophilin subfamily of Rab effector proteins. The protein forms a ternary complex with the small Ras-related GTPase Rab27A in its GTP-bound form and the motor protein myosin Va. A similar protein complex in mouse functions to tether pigment-producing organelles called melanosomes to the actin cytoskeleton in melanocytes, and is required for visible pigmentation in the hair and skin. A mutation in this gene results in Griscelli syndrome type 3, which is characterized by a silver-gray hair color and abnormal pigment distribution in the hair shaft. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

MLPH Gene-Disease associations (from GenCC):

• Griscelli syndrome type 3

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-237534764-G-C is Benign according to our data. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237534764-G-C is described in CliVar as Benign. Clinvar id is 1273815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLPH	NM_024101.7	c.1104+117G>C		intron_variant	Intron 9 of 15	ENST00000264605.8	NP_077006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLPH	ENST00000264605.8	c.1104+117G>C		intron_variant	Intron 9 of 15	1	NM_024101.7	ENSP00000264605.3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61089 AN: 151892 Hom.: 15260 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.298 AC: 209673 AN: 704512 Hom.: 34180 AF XY: 0.301 AC XY: 113437 AN XY: 376938

African (AFR) AF: 0.712 AC: 13255 AN: 18610

American (AMR) AF: 0.343 AC: 13579 AN: 39638

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 5408 AN: 20314

East Asian (EAS) AF: 0.370 AC: 12746 AN: 34466

South Asian (SAS) AF: 0.416 AC: 28829 AN: 69280

European-Finnish (FIN) AF: 0.230 AC: 10989 AN: 47792

Middle Eastern (MID) AF: 0.309 AC: 1263 AN: 4082

European-Non Finnish (NFE) AF: 0.258 AC: 112541 AN: 435750

Other (OTH) AF: 0.320 AC: 11063 AN: 34580

GnomAD4 genome AF: 0.403 AC: 61188 AN: 152008 Hom.: 15299 Cov.: 32 AF XY: 0.399 AC XY: 29648 AN XY: 74304

African (AFR) AF: 0.711 AC: 29495 AN: 41476

American (AMR) AF: 0.349 AC: 5322 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 892 AN: 3468

East Asian (EAS) AF: 0.403 AC: 2073 AN: 5148

South Asian (SAS) AF: 0.428 AC: 2061 AN: 4810

European-Finnish (FIN) AF: 0.220 AC: 2325 AN: 10566

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.264 AC: 17930 AN: 67960

Other (OTH) AF: 0.375 AC: 792 AN: 2112

Alfa AF: 0.143 Hom.: 237

Bravo AF: 0.422

Asia WGS AF: 0.434 AC: 1508 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.38
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2292885; hg19: chr2-238443407; COSMIC: COSV52825499;