chr17-63832807-G-A

Variant names:

• chr17-63832807-G-A
• rs2584622
• NM_001098426.2:c.*131C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098426.2(SMARCD2):​c.*131C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 770,020 control chromosomes in the GnomAD database, including 340,880 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.95 (68548 hom., cov: 32)
  • Exomes 𝑓: 0.94 (272332 hom.)
• Consequence: SMARCD2 NM_001098426.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 14 publications found

Genes affected

SMARCD2 (HGNC:11107): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SMARCD2 Gene-Disease associations (from GenCC):

• specific granule deficiency 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• specific granule deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098426.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD2	NM_001098426.2	MANE Select	c.*131C>T		3_prime_UTR	Exon 13 of 13	NP_001091896.1
	SMARCD2	NM_001330440.2		c.*131C>T		3_prime_UTR	Exon 13 of 13	NP_001317369.1
	SMARCD2	NM_001330439.1		c.*131C>T		3_prime_UTR	Exon 13 of 13	NP_001317368.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD2	ENST00000448276.7	TSL:1 MANE Select	c.*131C>T		3_prime_UTR	Exon 13 of 13	ENSP00000392617.2
	SMARCD2	ENST00000225742.13	TSL:1	c.*131C>T		3_prime_UTR	Exon 13 of 13	ENSP00000225742.9
	SMARCD2	ENST00000584483.6	TSL:2	n.2006C>T		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144322 AN: 152156 Hom.: 68487 Cov.: 32

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.947

GnomAD4 exome AF: 0.939 AC: 579821 AN: 617746 Hom.: 272332 Cov.: 8 AF XY: 0.939 AC XY: 304656 AN XY: 324286

African (AFR) AF: 0.982 AC: 15687 AN: 15968

American (AMR) AF: 0.964 AC: 28194 AN: 29236

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 17083 AN: 18288

East Asian (EAS) AF: 1.00 AC: 31841 AN: 31842

South Asian (SAS) AF: 0.974 AC: 58065 AN: 59600

European-Finnish (FIN) AF: 0.942 AC: 43330 AN: 45974

Middle Eastern (MID) AF: 0.928 AC: 2286 AN: 2464

European-Non Finnish (NFE) AF: 0.924 AC: 353789 AN: 382740

Other (OTH) AF: 0.934 AC: 29546 AN: 31634

GnomAD4 genome AF: 0.949 AC: 144442 AN: 152274 Hom.: 68548 Cov.: 32 AF XY: 0.952 AC XY: 70834 AN XY: 74444

African (AFR) AF: 0.983 AC: 40869 AN: 41562

American (AMR) AF: 0.953 AC: 14582 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3257 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5181 AN: 5182

South Asian (SAS) AF: 0.980 AC: 4728 AN: 4826

European-Finnish (FIN) AF: 0.941 AC: 9986 AN: 10612

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62730 AN: 68004

Other (OTH) AF: 0.947 AC: 2004 AN: 2116

Alfa AF: 0.940 Hom.: 67226

Bravo AF: 0.950

Asia WGS AF: 0.989 AC: 3440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		1.4
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: rs2584622; hg19: chr17-61910167;