rs2516781

Variant names:

• chr16-2035679-C-T
• rs2516781
• NM_001130012.3:c.415-645C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-2035679-C-T
• chr16-2035679-C-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001130012.3(NHERF2):​c.415-645C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 985,214 control chromosomes in the GnomAD database, including 43,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6618 hom., cov: 33)
  • Exomes 𝑓: 0.30 (36924 hom.)
• Consequence: NHERF2 NM_001130012.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21
• Publications: 7 publications found

Genes affected

NHERF2 (HGNC:11076): (NHERF family PDZ scaffold protein 2) This gene encodes a member of the NHERF family of PDZ scaffolding proteins. These proteins mediate many cellular processes by binding to and regulating the membrane expression and protein-protein interactions of membrane receptors and transport proteins. The encoded protein plays a role in intestinal sodium absorption by regulating the activity of the sodium/hydrogen exchanger 3, and may also regulate the cystic fibrosis transmembrane regulator (CFTR) ion channel. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 16-2035679-C-T is Benign according to our data. Variant chr16-2035679-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3911127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130012.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHERF2	NM_001130012.3	MANE Select	c.415-645C>T		intron	N/A	NP_001123484.1	Q15599-1
	NHERF2	NM_004785.6		c.415-645C>T		intron	N/A	NP_004776.3	Q15599-2
	NHERF2	NM_001252073.2		c.82-645C>T		intron	N/A	NP_001239002.1	Q15599-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHERF2	ENST00000424542.7	TSL:1 MANE Select	c.415-645C>T		intron	N/A	ENSP00000408005.2	Q15599-1
	NHERF2	ENST00000432365.6	TSL:1	c.415-645C>T		intron	N/A	ENSP00000402857.2	Q15599-2
	NHERF2	ENST00000901526.1		c.415-645C>T		intron	N/A	ENSP00000571585.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42977 AN: 151988 Hom.: 6599 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.297 AC: 247191 AN: 833108 Hom.: 36924 Cov.: 31 AF XY: 0.297 AC XY: 114139 AN XY: 384836

African (AFR) AF: 0.173 AC: 2730 AN: 15782

American (AMR) AF: 0.368 AC: 363 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 2287 AN: 5152

East Asian (EAS) AF: 0.379 AC: 1379 AN: 3636

South Asian (SAS) AF: 0.453 AC: 7463 AN: 16470

European-Finnish (FIN) AF: 0.268 AC: 76 AN: 284

Middle Eastern (MID) AF: 0.381 AC: 620 AN: 1626

European-Non Finnish (NFE) AF: 0.294 AC: 223897 AN: 761876

Other (OTH) AF: 0.307 AC: 8376 AN: 27296

GnomAD4 genome AF: 0.283 AC: 43040 AN: 152106 Hom.: 6618 Cov.: 33 AF XY: 0.289 AC XY: 21476 AN XY: 74356

African (AFR) AF: 0.182 AC: 7537 AN: 41510

American (AMR) AF: 0.321 AC: 4907 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1532 AN: 3468

East Asian (EAS) AF: 0.370 AC: 1915 AN: 5180

South Asian (SAS) AF: 0.479 AC: 2313 AN: 4828

European-Finnish (FIN) AF: 0.316 AC: 3346 AN: 10592

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20462 AN: 67938

Other (OTH) AF: 0.284 AC: 598 AN: 2104

Alfa AF: 0.301 Hom.: 7691

Bravo AF: 0.280

Asia WGS AF: 0.407 AC: 1414 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.1
DANN	Benign	0.73
PhyloP100		-1.2
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: rs2516781; hg19: chr16-2085680; COSMIC: COSV54594237; COSMIC: COSV54594237;