rs6991968

Variant names:

• chr8-38996101-G-A
• rs6991968
• NM_078473.3:c.227+112C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-38996101-G-A
• chr8-38996101-G-C
• chr8-38996101-G-T

Variant summary

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

The NM_078473.3(TM2D2):​c.227+112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,288,446 control chromosomes in the GnomAD database, including 115,074 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 0.44 (15084 hom., cov: 32)
  • Exomes 𝑓: 0.41 (99990 hom.)
• Consequence: TM2D2 NM_078473.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 7 publications found

Genes affected

TM2D2 (HGNC:24127): (TM2 domain containing 2) The protein encoded by this gene contains a structural module related to that of the seven transmembrane domain G protein-coupled receptor superfamily. This protein has sequence and structural similarities to the beta-amyloid binding protein (BBP), but, unlike BBP, it does not regulate a response to beta-amyloid peptide. This protein may have regulatory roles in cell death or proliferation signal cascades. This gene has multiple alternatively spliced transcript variants which encode two different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078473.3. 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
	TM2D2	NM_078473.3	MANE Select	c.227+112C>T		intron	N/A	NP_510882.1	Q9BX73-1
	TM2D2	NM_001024380.2		c.-291-307C>T		intron	N/A	NP_001019551.1	Q9BX73-2
	TM2D2	NM_001024381.2		c.-191+318C>T		intron	N/A	NP_001019552.1	Q9BX73-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM2D2	ENST00000456397.7	TSL:1 MANE Select	c.227+112C>T		intron	N/A	ENSP00000416050.2	Q9BX73-1
	TM2D2	ENST00000397070.6	TSL:1	c.-292+112C>T		intron	N/A	ENSP00000380260.2	Q9BX73-2
	TM2D2	ENST00000456845.6	TSL:1	c.-191+318C>T		intron	N/A	ENSP00000391674.2	Q9BX73-2

Frequencies

GnomAD3 genomes AF: 0.444 AC: 66797 AN: 150452 Hom.: 15064 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.413 AC: 470507 AN: 1137868 Hom.: 99990 AF XY: 0.410 AC XY: 229236 AN XY: 558544

African (AFR) AF: 0.427 AC: 10924 AN: 25578

American (AMR) AF: 0.531 AC: 11621 AN: 21878

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 7747 AN: 18252

East Asian (EAS) AF: 0.715 AC: 24559 AN: 34326

South Asian (SAS) AF: 0.323 AC: 19988 AN: 61804

European-Finnish (FIN) AF: 0.462 AC: 19381 AN: 41974

Middle Eastern (MID) AF: 0.425 AC: 2085 AN: 4910

European-Non Finnish (NFE) AF: 0.402 AC: 353660 AN: 880626

Other (OTH) AF: 0.423 AC: 20542 AN: 48520

GnomAD4 genome AF: 0.444 AC: 66861 AN: 150578 Hom.: 15084 Cov.: 32 AF XY: 0.449 AC XY: 33048 AN XY: 73600

African (AFR) AF: 0.437 AC: 17514 AN: 40104

American (AMR) AF: 0.520 AC: 7927 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3470

East Asian (EAS) AF: 0.744 AC: 3831 AN: 5152

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4820

European-Finnish (FIN) AF: 0.475 AC: 5014 AN: 10558

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27797 AN: 67938

Other (OTH) AF: 0.456 AC: 957 AN: 2098

Alfa AF: 0.434 Hom.: 4897

Bravo AF: 0.448

Asia WGS AF: 0.510 AC: 1776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.68
PhyloP100		-0.20
PromoterAI		0.0096	Neutral
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: rs6991968; hg19: chr8-38853620;